Skip to main content

Advertisement

SpringerLink
Log in

Decreased prostasin expression is associated with aggressiveness of oral squamous cell carcinoma

  • Research Article
  • Published:
Human Cell Aims and scope Submit manuscript

Abstract

Prostasin is a glycosylphosphatidylinositol-anchored serine protease widely expressed in epithelial cells, with crucial epidermal barrier functions. Evidence has suggested prostasin may have served as a tumor suppressor in various cancers, but its role in oral squamous cell carcinoma (OSCC) remains unclear. Thus, herein, we conducted an immunohistochemical prostasin study in 119 resected OSCC cases. Prostasin expression was decreased in 63% (75/119) of cases. OSCC with decreased prostasin immunoreactivity (low prostasin cases) tended to show a higher histological grade (p = 0.0088) and a more infiltrative cancer cell morphology (p = 0.0024). We then explored the role of prostasin in the OSCC cell lines: SAS and HSC-4. SAS did not express detectable prostasin levels, whereas HSC-4 expressed low but distinct levels. Prostasin overexpression suppressed the proliferation and migration of both OSCC lines in vitro. Conversely, prostasin silencing significantly enhanced growth rates of HSC-4. Finally, we analyzed the impact of prostasin expression on the prognosis of patients with OSCC; decreased expression tended to correlate with shorter overall survival (p = 0.0291) after resection. This trend was supported by our analyses using a public database (Kaplan–Meier plotter) of head and neck squamous cell carcinomas. In conclusion, we showed decreased prostasin expression was associated with aggressive features and a poorer prognosis of OSCC.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5
Fig. 6
Fig. 7

Similar content being viewed by others

References

  1. Yu JX, Chao L, Chao J. Prostasin is novel human serine protease from seminal fluid. Purification, tissue distribution, and localization in prostate gland. J Biol Chem. 1994;269:18843–8.

    Article  CAS  Google Scholar 

  2. Tamir A, Gangadharan A, Balwani S, et al. The serine protease prostasin (PRSS8) is a potential biomarker for early detection of ovarian cancer. J Ovarian Res. 2016;31:9–20.

    Google Scholar 

  3. Vallet V, Chraibi A, Gaeggeler HP, Horisberger JD, Rossier BC. An epithelial serine protease activates the amiloride-sensitive sodium channel. Nature. 1997;389:607–10.

    Article  CAS  Google Scholar 

  4. Bruns JB, Carattino MD, Sheng S, et al. Epithelial Na+ channels are fully activated by furin- and prostasin-dependent release of an inhibitory peptide from the gamma subunit. J Biol Chem. 2007;282:6153–60.

    Article  CAS  Google Scholar 

  5. Leyvraz C, Charles RP, Rubera I, et al. The epidermal barrier function is dependent on the serine protease CAP1/Prss8. J Cell Biol. 2005;170:487–96.

    Article  CAS  Google Scholar 

  6. Hummler E, Dousse A, Rieder A, et al. The channel-activating protease CAP1/PRSS8 is required for placental labyrinth maturation. PLoS ONE. 2013;8: e55796.

    Article  CAS  Google Scholar 

  7. Chen LM, Chai KX. Prostasin serine protease inhibitors breast cancer invasiveness and is transcriptionally regulated by promoter DNA methylation. Int J Cancer. 2002;97:323–9.

    Article  CAS  Google Scholar 

  8. Sakashita K, Mimori K, Tanaka F, et al. Clinical significance of low expression of prostasin mRNA in human gastric cancer. J Surg Oncol. 2008;98:559–64.

    Article  CAS  Google Scholar 

  9. Bao Y, Li K, Guo Y, et al. Tumor suppressor PRSS8 targets Sphk1/S1P/Stat3/Akt signaling in colorectal cancer. Oncotarget. 2016;7:26780–92.

    Article  Google Scholar 

  10. Ma C, Ma W, Zhou N, Chen N, An L, Zhang Y. Protease serine S1 family member 8 (PRSS8) inhibits tumor growth in vitro and in vivo in human non-small cell lung cancer. Oncol Res. 2017;25:781–7.

    Article  Google Scholar 

  11. Bao Y, Wang Q, Guo Y, et al. PRSS8 methylation and its significance in esophageal squamous cell carcinoma. Oncotarget. 2016;7:28540–55.

    Article  Google Scholar 

  12. Zhang L, Jia G, Shi B, Ge G, Duan H, Yang Y. PRSS8 is downregulated and suppresses tumour growth and metastases in hepatocellular carcinoma. Cell Physiol Biochem. 2016;40:757–69.

    Article  CAS  Google Scholar 

  13. Yang HY, Fang DZ, Ding LS, Hui XB, Liu D. Overexpression of prostate serine 8 inhibits glioma cell proliferation, migration, and invasion via suppressing the Akt/mTOR signaling pathway. Oncol Res. 2017;25:923–30.

    Article  Google Scholar 

  14. Yamamoto K, Kawaguchi M, Shimomura T, et al. Hepatocyte growth factor activator inhibitor type-2 (HAI-2)/SPINT2 contributes to invasive growth of oral squamous cell carcinoma cells. Oncotarget. 2018;9:11691–706.

    Article  Google Scholar 

  15. Jou A, Hess J. Epidemiology and molecular biology of head and neck cancer. Oncol Res Treat. 2017;40:328–32.

    Article  CAS  Google Scholar 

  16. Shield KD, Ferlay J, Jemal A. The global incidence of lip, oral cavity, and pharyngeal cancers by subsite in 2012. CA Cancer J Clin. 2017;67:51–64.

    Article  Google Scholar 

  17. Chinn SB, Myers JN. Oral cavity carcinoma: current management, controversies, and future directions. Oral Oncol. 2015;33:3269–76.

    CAS  Google Scholar 

  18. Bryne M, Jenssen N, Boysen M. Histological grading in the deep invasive front of T1 and T2 glottic squamous cell carcinomas has high prognostic value. Virchows Arch. 1995;427:277–81.

    Article  CAS  Google Scholar 

  19. Hou GX, Liu P, Yang J, Wen S. Mining expression and prognosis of topoisomerase isoforms in non-small-cell lung cancer by using Oncomine and Kaplan-Meier plotter. PLoS ONE. 2017;12: e0174515.

    Article  Google Scholar 

  20. Nagy A, Munkacsy G, Gyorffy B. Pancancer survival analysis of cancer hallmark genes. Sci Rep. 2021;11:6047. https://doi.org/10.1038/s41598-021-84787-5.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  21. Tamir A, Gangadharan A, Balwani S, et al. The serine protease prostasin (PRSS8) is a potential biomarker for early detection of ovarian cancer. J Ovarian Res. 2016;9:1–13.

    Article  Google Scholar 

  22. Chen LM, Zhang X, Chai KX. Regulation of prostasin expression and function in the prostate. Prostate. 2004;59:1–12.

    Article  CAS  Google Scholar 

  23. Chen LM, Verity NJ, Chai KX. Loss of prostasin (PRSS8) in human bladder transitional cell carcinoma cell lines is associated with epithelial-mesenchymal transition (EMT). BMC Cancer. 2009;9:377.

    Article  Google Scholar 

  24. Bao Y, Guo Y, Yang Y, Wei X, et al. PRSS8 suppresses colorectal carcinogenesis and metastasis. Oncogene. 2019;38:497–517.

    Article  CAS  Google Scholar 

Download references

Acknowledgements

We thank Ms. J. Kurogi and A. Nishida for their skilled technical assistance. The authors also thank Enago (www.enago.jp) for English review.

Funding

This work was supported by Japan Society for the Promotion of Science KAKENHI 20K18483 (K.Y.) and 17K08764 (T.F.) and by a Grant for Clinical Research from Miyazaki University Hospital.

Author information

Author notes

  1. Koji Yamamoto and Fumiki Yamashita contributed equally to this study.

Authors and Affiliations

  1. Section of Oncopathology and Regenerative Biology, Department of Pathology, Faculty of Medicine, University of Miyazaki, 5200 Kihara, Kiyotake, Miyazaki, Japan

    Koji Yamamoto, Fumiki Yamashita, Makiko Kawaguchi, Aya Izumi, Takumi Kiwaki, Hiroaki Kataoka & Tsuyoshi Fukushima

  2. Department of Oral and Maxillofacial Surgery, Faculty of Medicine, University of Miyazaki, Miyazaki, Japan

    Takeshi Kaneuji & Yoshihiro Yamashita

Authors
  1. Koji Yamamoto
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Fumiki Yamashita
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Makiko Kawaguchi
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Aya Izumi
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Takumi Kiwaki
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Hiroaki Kataoka
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Takeshi Kaneuji
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Yoshihiro Yamashita
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Tsuyoshi Fukushima
    View author publications

    You can also search for this author in PubMed Google Scholar

Contributions

KY and FY performed experiments, collected samples, performed analyses, and drafted the manuscript. MK, AI, and TK analyzed data and discussed experimental design and results. HK discussed experimental design. TK and YY collected samples and contributed to patient management. TF designed experiments, discussed experimental design and results, analyzed data, and contributed to the writing of the final manuscript.

Corresponding author

Correspondence to Tsuyoshi Fukushima.

Ethics declarations

Conflict of interest

The authors declare no competing interests.

Ethical approval

The study protocol was performed in accordance with the revised Helsinki Declaration of 2008 and approved by the Institutional Review Board of the Faculty of Medicine, University of Miyazaki (ethics approval number: 2014-006).

Informed consent

Opt-out consent was applied during this study.

Additional information

Publisher's Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Supplementary Information

Below is the link to the electronic supplementary material.

Supplementary file1 (PDF 93 KB)

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Yamamoto, K., Yamashita, F., Kawaguchi, M. et al. Decreased prostasin expression is associated with aggressiveness of oral squamous cell carcinoma. Human Cell 34, 1434–1445 (2021). https://doi.org/10.1007/s13577-021-00575-3

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s13577-021-00575-3

Keywords

Search

Navigation